Pyrrolidine analgesic



Patented Oct. 6, 1953 2,654,764 PYRROLIDINE ANALGESIC Carl von Seemannand Gordon A. Grant, Montreal, Quebec, Canada, McKenna & Harrison,Quebec, Canada, a corp assignors to Ayerst, Limited, St. Laurent,

oration oi Canada No Drawing. Application September 12, 1950, Serial N0. 184,517. In Canada August 28, 1950 1 Claim. (01. 260-326.5)

This invention relates to a new chemical compound which is eifective asa sedative.

The new compound is 2,4-dioxo-3-ethyl-3- 8- thoxyethyD-pyrrolidine ofthe general formula CzHs o=o o CHzCHgOCzHi H2 According to the inventionthis compound is prepared by reacting an alkyla-CthYl-a-(fiethoxyethyl)' -halogen-acetoacetate with ammonia,preferably in the presence of a mutual solvent, for example alcohol, bychoice methyl alcohol. The solvent is preferably anhydrous.

The reaction is carried out in a closed system to prevent the escape ofthe ammonia. The preferred acetoacetate is ethyla-ethyl-a-(B-ethoxyethyl) -bromo-acetoacetate (T. S. Work, Jour. Chem.Soc. 1946, 194).

The charge is heated preferably to a temperature within the range fromabout 65 C. to about 66 C. for about 24 hours. The charge is then cooledand the solvent is evaporated in vacuo. 2,4 dioxo 3 ethyl 3 (13ethoxyethyD- pyrrolidine and ammonium bromide are formed in thereaction, and remain as a residual mixture after evaporation.

The pyrrolidine may be extracted from the residual mixture with asolvent, hexane preferred, the extract evaporated and the residuedistilled in vacuo to yield the crude pyrrolidine in crystalline form.The latter can be recrystallized from hexane and the pure substanceobtained as colorless crystals.

The new compounds have highly efiective sedative properties and lowtoxicity. They are highly soluble in water and thus are ingestedrapidly. The active substance may be put up in dosage units for exampletablets or capsules. In the case of a tablet the substance should bemixed with an excipient, for example lactose or starch.

Example In order to further demonstrate the invention, the followingspecific example will be given of one method of its operation.

Ethyl a-ethyl-u-(p-ethoxyethyl) 7-bIOlIl0-fl0- etoacetate (1.5 g.) wasdissolved in a mixture of 45 cc. anhydrous methanol and 11 g. of liquidammonia (which can be prepared by introducing ammonia gas into thealcohol with cooling in Dry Ice). The container was sealed and heated toC. to 66 C. for 24 hours. The contents were then cooled in ice and thesolvents evaporated in vacuo. The residue was continuously extractedwith hexane in order to separate 2,4- dioxo 3 ethyl 3 (B ethoxyethyl)pyrrolidine from the accompanying ammonium bromide. The hexane extractswere evaporated and the residue distilled in vacuo, yielding the crude2,4-dioxo-3-ethyl-3-(B-ethoxyethyl) -pyrrolidine in crystalline form.The latter was recrystallized from hexane and the pure substance 2,4dioxo 3 ethyl 3 (,8 ethoxyethyD- pyrrolidine obtained in colourlesscrystals, M. P. 81.5 C.82.5 C. It is freely soluble in water, loweralcohols, acetone and ethylene dichloride and moderately soluble inhexane.

For C10H17O3N (199) Calculated: C, 60.26% H: 8.60% N: 7.03%

Found: C, 59.87% H: 8.33% N: 7.24%

60.17% 8.58% This compound was found to have sedative properties.

We claim:

The compound 2,4-dioxo-3-ethyl-3-(,B-ethoxyethyl) -pyrrolidine.

CARL VON SEEMANN. GORDON A. GRANT.

Number Name Date Schnider Aug. 31, 1943

